The proposed training and research will be conducted at the SRPRC and the University of Texas Health Science Center at San Antonio. Dr. Erika Honore is seeking SERCA support to advance her development as an independent investigator in comparative medicine, with emphasis on models for women's health. Dr. Honore has completed a postdoctoral fellowship at Wake Forest University studying estrogens and atherosclerosis in macaques. As part of the current proposal, she will receive further training and guidance from investigators in genetics, cardiology and reproductive endocrinology. Studies will utilize a well characterized, pedigreed colony of more than 250 female baboons to establish a NHP model of naturally occurring perimenopause and menopause. Postmenopausal women are at increased risk for cardiovascular disease and osteoporosis, as well as other conditions. Hormone replacement therapy (HRT) effectively reduces the risk, but only a fraction of U.S. women receive HRT. Research into menopause and HRT has relied on surgically ovariectomized NHPs as models of menopause. This does not adequately reflect the condition in women, where ovarian function declines gradually over several years and the postmenopausal ovary continues to produce androgens. Pilot data from the SRPRC indicate that aging female baboons undergo a natural transition into menopause with hormonal and physiological changes similar to those seen in women. The specific aims of this proposal are: 1) to characterize the perimenopausal period; 2) to determine the hormonal profiles of pre-, peri- and postmenopausal females; 3) to longitudinally assess relevant physiological variables in these three cohorts. These aims will be achieved through menstrual cycle analysis, assays of annual blood samples for hormones and lipoproteins, ultrasound measurements of peripheral vascular reactivity, and radiographic measurements of bone density. Interventional studies of novel HRT regimens are proposed for years 4 and 5 with the goal of increasing national compliance with HRT by developing an acceptable alternative.